Long Noncoding RNA (lncRNA) Small Nucleolar RNA Host Gene 5 (SNHG5) Regulates Proliferation, Differentiation, and Apoptosis of K562 Cells in Chronic Myeliod Leukemia

Abstract

BackgroundHuman chronic myelogenous leukemia (CML) is a hematopoietic stem cell disorder with high malignant and invasive activity. lncRNA SNHG5 has been reported to be upregulated in CML. However, whether it affects the proliferation, differentiation, and apoptosis in CML cells is still unknown. This study investigated the role of SNHG5 in CML and revealed the potential mechanism.Material/MethodsK562 cells were transfected with shRNA, and the expression level of SNHG5 was assessd by quantitative RT-PCR. The proliferation ability was determined by CCK-8 assay. Western blot analysis was performed to detect protein expressions related to cell proliferation, differentiation, and apoptosis. Cell apoptosis rate was analyzed by flow cytometry. The DNA methylation level was determined by methylation-specific PCR (MSP).ResultsOur results show that inhibition of SNHG5 induced by RNA interference significantly inhibits K562 cells proliferation and induces cell differentiation with the increased expression of CD42b, CD11b, CD14, GATA-1, and β-globin. Flow cytometry analysis indicated that inhibition of SNHG5 significantly induced cell apoptosis with decreased expression of Bcl-2 and increased expression of Bax and cleaved capase-3. Additionally, Western blot and MSP analyses confirmed that inhibition of SNHG5 increased the expression of DR4 gene through suppressing its methylation.ConclusionsInhibition of SNHG5 suppressed K562 cell proliferation through inducing the differentiation and apoptosis by inhibiting methylation of DR4. Therefore, downregulated SNHG5 could play a key role in CML progression, and might provide a new strategy for the treatment of CML.

<p>Latest Advances of Long Non-Coding RNA SNHG5 in Human Cancers</p>

“…14 Interestingly, DR4, an oncogene in the occurrence and development of tumors, was also involved in functional process of SNHG5. 22 In conclusion, these composite findings confirmed the imbalance of SNHG5 in AML and CML, forecasting its potential application in chemosensitivity.…”

“…21 Ma et al reported that the effect of SNHG5 on bladder cancer cells was partially involved with targeting p27. 23 Moreover, the methylation and downregulation of DR4 could also be induced by SNHG5 22 (Figure 3).…”

“…14 Further investigation demonstrated that inhibition of SNHG5 suppressed cell proliferation and induced differentiation, apoptosis of CML cells. 22 Subsequent mechanical investigation showed that SNHG5 could serve as a ceRNA sponging miR-205-5p to regulate imatinib resistance. 14 Interestingly, DR4, an oncogene in the occurrence and development of tumors, was also involved in functional process of SNHG5.…”

“…11,13,17,20 Surprisingly, Zhao et al also verified that several biological molecules or proteins, such as metastasisassociated genes protein 2 (MTA2), spermatogenesis associated serine rich 2 (SPATS2), p27 and TRAIL-R1 (DR4) were involved in the functional process of SNHG5. 10,[21][22][23] In this review, we generalized the latest progress in the expression, function and regulation of lncRNA SNHG5 in multiple human cancers (Table 1-2) and further explored its potential role as a clinical biomarker and therapeutic target for cancers ( Figure 1-3).…”

The role of long non‐coding RNAs and downstream signaling pathways in leukemia progression

“…B Gao et al reported that inhibition of SNHG5 significantly inhibits K562 cell proliferation and induces cell differentiation by increasing the expression of CD42b, CD11b, CD14, GATA‐1, and β‐globin, also increases the expression of DR4 gene by inhibiting its methylation. They also found that by decreasing the expression of Bcl‐2 and increasing the expression of Bax and cleaved caspase‐3, SNHG5 significantly promotes cell apoptosis 50 …”